title: Stromal derived growth factor-1 (CXCL12) modulates synaptic transmission to immature neurons during post-ischemic cerebral repair.
abstract: In response to ischemic injury, the brain mounts a repair process involving the development of new neurons, oligodendrocytes, and astrocytes. However, the manner in which new neurons integrate into existing brain circuitry is not well understood. Here we observed that during the four weeks after transient middle cerebral artery occlusion (MCAO), doublecortin (DCX)-expressing neural progenitors originating in the subventricular zone (SVZ) were present in the ischemic lesion borderzone, where they received γ-aminobutyric acid (GABA) inputs, a feature that is common to newly developing neurons. The chemokine stromal derived factor-1 (SDF-1 or CXCL12) was enriched in lesional endothelial and microglial cells for up to four weeks after transient MCAO, and application of SDF-1 to acute brain slices enhanced GABAergic inputs to the new neurons. These observations suggest that SDF-1 is in a position to coordinate neovascularization and neurogenesis during the repair process after cerebral ischemia-reperfusion.
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL, USA; Department of Surgery (Neurosurgery), University of Chicago, Chicago, IL, USA. Electronic address: aardelt@neurology.bsd.uchicago.edu.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Ardelt
authors.forename: Bula J
authors.initials: BJ
authors.lastname: Bhattacharyya
authors.forename: Abdelhak
authors.initials: A
authors.lastname: Belmadani
authors.forename: Dongun
authors.initials: D
authors.lastname: Ren
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D042783:Endothelial Cells / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D054377:Chemokine CXCL12; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
keywords: ACSF; Animal models; BIC; Brain ischemia; CCA; CXC chemokine receptor 4; CXCR4; Chemokines; DCX; DG; ECA; EGFP; Electrophysiology; GABA; GFAP; ICA; MCA; MCAO; Neuroregeneration; PBS; PFA; SDF-1; SGZ; SVZ; TTX; artificial CSF; bicuculline methiodide; common carotid artery; dentate gyrus; doublecortin; enhanced green fluorescent protein; external carotid artery; glial fibrillary acidic protein; internal carotid artery; mRFP; middle cerebral artery; middle cerebral artery occlusion; monomeric red fluorescent protein; paraformaldehyde; phosphate buffered saline; stromal derived factor-1 (CXCL12); subgranular zone; subventricular zone; tetrodotoxin; vWF; von Willebrand factor; γ-aminobutyric acid